Transferrin (Tf) is a promising candidate for targeted drug delivery. While development of such products is impossible without the ability to monitor biodistribution of Tf-drug conjugates in tissues and reliable measurements of their levels in blood and other biological fluids, the presence of very abundant endogenous Tf presents a significant impediment to such efforts. Several non-cognate metals have been evaluated in this work as possible tracers of exogenous transferrin in complex biological matrices using inductively coupled plasma mass spectrometry (ICP MS) as a detection tool. Placing Ni(II) on a His-tag of recombinant Tf resulted in formation of a marginally stable protein-metal complex, which readily transfers the metal to ubiquitous physiological scavengers, such as serum albumin. An alternative strategy targeted iron-binding pockets of Tf, where cognate Fe(III) was replaced metal ions known to bind this protein. Both Ga(III) and In(III) were evaluated, with the latter being vastly superior as a tracer (stronger binding to Tf unaffected by the presence of metal scavengers and the retained ability to associate with Tf receptor). Spiking serum with indium-loaded Tf followed by ICP MS detection demonstrated that protein quantities as low as 0.04 nM can be readily detected in animal blood. Combining laser ablation with ICP MS detection allows distribution of exogenous Tf to be mapped within animal tissue cross-sections with spatial resolution exceeding 100 μm. The method can be readily extended to a range of other therapeutics where metalloproteins are used as either carriers or payloads.

We optimize a flexible electronic composite film by hybridizing the polydimethylsiloxane (PDMS) substrate with hydrophobic nano-SiO2 particles. We then detect the mismatch strain from experiments based on the digital-image correlation method and explore the effect of the substrate nano-SiO2 mass fraction on the strain mismatch over a wide temperature range. The strain mismatch coefficient (SMC) is proposed to better evaluate the degree of strain mismatch between the metal interconnect and the hybrid substrate. Experimental results show that pure PDMS results in relatively large temperature-induced SMC values than nano-SiO2 hybridized substrates and hybridization of nano-SiO2 particles significantly decreases the film SMC value. At a constant temperature, e.g., 20 °C, the SMC value is observed to decrease as the mass fraction of nano-SiO2 in the flexible substrate increases, which turns to be the lowest SMC value as the content of nano-SiO2 reaches 8 wt. %. Finally, by testing the degree of interconnect buckling using atomic force microscopy, our experimental results are verified.

The stress distribution of the two-dimensional (2D) horseshoe-shaped interconnect in the flexible electronic composite film under thermal load is reported, and the effect of substrate nano-SiO 2 hybridization on this stress distribution is studied. Experimental results show that when the temperature rises, stress concentration gradually occurs at the edge of the 2D horseshoe-shaped interconnect. After nano-SiO 2 hybridizing, the stress concentration at the edge is significantly reduced, and the strain stability near the edge is improved. When the substrate SiO 2 content is greater than 8 wt%, the negative effect of thermal stress on the composite film is reduced to a very low level.

No abstract

No abstract